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Item Comparative Effectiveness of 2 Interventions to Increase Breast, Cervical, and Colorectal Cancer Screening Among Women in the Rural US: A Randomized Clinical Trial(American Medical Association, 2023-04-02) Champion, Victoria L.; Paskett, Electra D.; Stump, Timothy E.; Biederman, Erika B.; Vachon, Eric; Katz, Mira L.; Rawl, Susan M.; Baltic, Ryan D.; Kettler, Carla D.; Seiber, Eric E.; Xu, Wendy Y.; Monahan, Patrick O.; Biostatistics and Health Data Science, School of MedicineImportance: Women living in rural areas have lower rates of breast, cervical, and colorectal cancer screening compared with women living in urban settings. Objective: To assess the comparative effectiveness of (1) a mailed, tailored digital video disc (DVD) intervention; (2) a DVD intervention plus telephonic patient navigation (DVD/PN); and (3) usual care with simultaneously increased adherence to any breast, cervical, and colorectal cancer screening that was not up to date at baseline and to assess cost-effectiveness. Design, setting, and participants: This randomized clinical trial recruited and followed up women from rural Indiana and Ohio (community based) who were not up to date on any or all recommended cancer screenings. Participants were randomly assigned between November 28, 2016, and July 1, 2019, to 1 of 3 study groups (DVD, DVD/PN, or usual care). Statistical analyses were completed between August and December 2021 and between March and September 2022. Intervention: The DVD interactively assessed and provided messages for health beliefs, including risk of developing the targeted cancers and barriers, benefits, and self-efficacy for obtaining the needed screenings. Patient navigators counseled women on barriers to obtaining screenings. The intervention simultaneously supported obtaining screening for all or any tests outside of guidelines at baseline. Main outcomes and measures: Receipt of any or all needed cancer screenings from baseline through 12 months, including breast, cervical, and colorectal cancer, and cost-effectiveness of the intervention. Binary logistic regression was used to compare the randomized groups on being up to date for all and any screenings at 12 months. Results: The sample included 963 women aged 50 to 74 years (mean [SD] age, 58.6 [6.3] years). The DVD group had nearly twice the odds of those in the usual care group of obtaining all needed screenings (odds ratio [OR], 1.84; 95% CI, 1.02-3.43; P = .048), and the odds were nearly 6 times greater for DVD/PN vs usual care (OR, 5.69; 95% CI, 3.24-10.5; P < .001). The DVD/PN intervention (but not DVD alone) was significantly more effective than usual care (OR, 4.01; 95% CI, 2.60-6.28; P < .001) for promoting at least 1 (ie, any) of the needed screenings at 12 months. Cost-effectiveness per woman who was up to date was $14 462 in the DVD group and $10 638 in the DVD/PN group. Conclusions and relevance: In this randomized clinical trial of rural women who were not up to date with at least 1 of the recommended cancer screenings (breast, cervical, or colorectal), an intervention designed to simultaneously increase adherence to any or all of the 3 cancer screening tests was more effective than usual care, available at relatively modest costs, and able to be remotely delivered, demonstrating great potential for implementing an evidence-based intervention in remote areas of the midwestern US.Item Exceptional Response with Immunotherapy in a Patient with Anaplastic Thyroid Cancer(AlphaMed Press, 2017-10) Kollipara, Revathi; Schneider, Bryan; Radovich, Milan; Babu, Sunil; Kiel, Patrick J.; Medicine, School of MedicineChemotherapy with or without radiation is the standard therapy for anaplastic thyroid cancer (ATC), although the response rate is not high and not durable. We describe a 62-year-old male who was diagnosed with ATC and initially treated with a thyroidectomy and lymph node dissection, followed by chemotherapy. Next generation sequencing was then performed to guide therapy and the tumor was found to have BRAF and programmed death-ligand 1 (PD-L1) positivity that was subsequently treated with vemurafenib and nivolumab. This led to substantial regression of tumor nodules. Genomic sequencing-based approaches to identify therapeutic targets has potential for improving outcomes. Currently, the patient continues to be in complete radiographic and clinical remission 20 months after beginning treatment with nivolumab. KEY POINTS: Programmed death-1 (PD-1)/PD-L1 immunotherapy has shown evidence of durable responses in certain malignancies such as melanoma, lung cancer, and renal cell carcinoma.PD-L1 positive tumors promote autoimmunity against the tumor; therefore, PD-1/PD-L1 blockade may be beneficial.Molecular profiling could possibly result in improved targeted therapy for certain malignancies.Item Fear of Palliative Care: Roles of Age and Depression Severity(Mary Ann Liebert, 2022) Alonzi, Sarah; Perry, Laura M.; Lewson, Ashley B.; Mossman, Brenna; Silverstein, Madison W.; Hoerger, Michael; Psychology, School of ScienceBackground: Palliative care is underutilized due in part to fear and misunderstanding, and depression might explain variation in fear of palliative care. Objective: Informed by the socioemotional selectivity theory, we hypothesized that older adults with cancer would be less depressed than younger adults, and subsequently less fearful of utilizing palliative care. Setting/Subjects: Patients predominately located in the United States with heterogeneous cancer diagnoses (n = 1095) completed the Patient-Reported Outcomes Information System (PROMIS) Depression scale and rated their fear of palliative care using the Palliative Care Attitudes Scale (PCAS). We examined the hypothesized intercorrelations, followed by a bootstrapped analysis of indirect effects in the PROCESS macro for SPSS. Results: Participants ranged from 26 to 93 years old (mean [M] = 60.40, standard deviation = 11.45). The most common diagnoses were prostate (34.1%), breast (23.3%), colorectal (17.5%), skin (15.3%), and lung (13.5%) cancer. As hypothesized, older participants had lower depression severity (r = −0.20, p < 0.001) and were less fearful of palliative care (r = −0.11, p < 0.001). Participants who were more depressed were more fearful of palliative care (r = 0.21, p < 0.001). An indirect effect (β = −0.04, standard error = .01, 95% confidence interval: −0.06 to −0.02) suggested that depression severity may account for up to 40% of age-associated differences in fear of palliative care. Conclusions: Findings indicate that older adults with cancer are more likely to favor palliative care, with depression symptom severity accounting for age-related differences. Targeted interventions among younger patients with depressive symptoms may be helpful to reduce fear and misunderstanding and increase utilization of palliative care.Item Increased spatial dimensions of repetitive heat and cold stimuli in older women(Wolters Kluwer, 2017-05) Naugle, Kelly M.; Cruz-Almeida, Yenisel; Fillingim, Roger B.; Staud, Roland; Riley, Joseph L., III; Kinesiology, School of Physical Education and Tourism ManagementProtocols of temporal summation (TS) of pain typically involve the delivery of brief repetitive noxious pulses of a constant intensity while measuring the perceived intensity of pain after each pulse. The size percept of noxious repetitive stimulation has been poorly characterized. Furthermore, no studies have investigated age differences in TS of cold pain. The current study examined TS of pain intensity and the perceived size of the painful area during repetitive noxious heat and cold pulses in healthy younger (n = 104) and older adults (n = 40). Trials of 10 brief repetitive noxious heat or cold pulses were delivered to the upper extremities. Participants rated the perceived size of the painful area or intensity of pain after each pulse. The magnitude of change for the size percept and intensity for pain were calculated for each trial. The results indicated that older adults experienced greater TS of the size percept of cold stimuli compared with younger adults. Additionally, older women experienced greater TS of the size percept of heat stimuli compared with older men and all younger participants. No overall age or sex differences were found in the TS of pain intensity for cold or heat trials. These results suggest dysfunctional modulation of the spatial percept of the painful stimuli by older adults, and in particular older women, during repetitive noxious thermal pulses.Item A multimodality test to guide the management of patients with a pancreatic cyst(American Association for the Advancement of Science, 2019-07-17) Springer, Simeon; Masica, David L.; Dal Molin, Marco; Douville, Christopher; Thoburn, Christopher J.; Afsari, Bahman; Li, Lu; Cohen, Joshua D.; Thompson, Elizabeth; Allen, Peter J.; Klimstra, David S.; Schattner, Mark A.; Schmidt, C. Max; Yip-Schneider, Michele; Simpson, Rachel E.; Castillo, Carlos Fernandez-Del; Mino-Kenudson, Mari; Brugge, William; Brand, Randall E.; Singhi, Aatur D.; Scarpa, Aldo; Lawlor, Rita; Salvia, Roberto; Zamboni, Giuseppe; Hong, Seung-Mo; Hwang, Dae Wook; Jang, Jin-Young; Kwon, Wooil; Swan, Niall; Geoghegan, Justin; Falconi, Massimo; Crippa, Stefano; Doglioni, Claudio; Paulino, Jorge; Schulick, Richard D.; Edil, Barish H.; Park, Walter; Yachida, Shinichi; Hijioka, Susumu; van Hooft, Jeanin; He, Jin; Weiss, Matthew J.; Burkhart, Richard; Makary, Martin; Canto, Marcia I.; Goggins, Michael G.; Ptak, Janine; Dobbyn, Lisa; Schaefer, Joy; Sillman, Natalie; Popoli, Maria; Klein, Alison P.; Tomasetti, Cristian; Karchin, Rachel; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Wolfgang, Christopher L.; Hruban, Ralph H.; Lennon, Anne Marie; Surgery, School of MedicinePancreatic cysts are common and often pose a management dilemma, because some cysts are precancerous, whereas others have little risk of developing into invasive cancers. We used supervised machine learning techniques to develop a comprehensive test, CompCyst, to guide the management of patients with pancreatic cysts. The test is based on selected clinical features, imaging characteristics, and cyst fluid genetic and biochemical markers. Using data from 436 patients with pancreatic cysts, we trained CompCyst to classify patients as those who required surgery, those who should be routinely monitored, and those who did not require further surveillance. We then tested CompCyst in an independent cohort of 426 patients, with histopathology used as the gold standard. We found that clinical management informed by the CompCyst test was more accurate than the management dictated by conventional clinical and imaging criteria alone. Application of the CompCyst test would have spared surgery in more than half of the patients who underwent unnecessary resection of their cysts. CompCyst therefore has the potential to reduce the patient morbidity and economic costs associated with current standard-of-care pancreatic cyst management practices.Item Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel(American Medical Association, 2021-01-01) Kunkle, Brian W.; Schmidt, Michael; Klein, Hans-Ulrich; Naj, Adam C.; Hamilton-Nelson, Kara L.; Larson, Eric B.; Evans, Denis A.; De Jager, Phil L.; Crane, Paul K.; Buxbaum, Joe D.; Ertekin-Taner, Nilufer; Go, Rodney C.P.; Obisesan, Thomas O.; Kamboh, Ilyas; Bennett, David A.; Hall, Kathleen S.; Goate, Alison M.; Foroud, Tatiana M.; Martin, Eden R.; Wang, Li-Sao; Byrd, Goldie S.; Farrer, Lindsay A.; Haines, Jonathan L.; Schellenberg, Gerard D.; Mayeux, Richard; Pericak-Vance, Margaret A.; Reitz, Christiane; Graff-Radford, Neill R.; Martinez, Izri; Ayodele, Temitope; Logue, Mark W.; Cantwell, Laura B.; Jean-Francois, Melissa; Kuzma, Amanda B.; Adams, L.D.; Vance, Jeffery M.; Cuccaro, Michael L.; Chung, Jaeyoon; Mez, Jesse; Lunetta, Kathryn L.; Jun, Gyungah R.; Lopez, Oscar L.; Hendrie, Hugh C.; Reiman, Eric M.; Kowall, Neil W.; Leverenz, James B.; Small, Scott A.; Levey, Allan I.; Golde, Todd E.; Saykin, Andrew J.; Starks, Takiyah D.; Albert, Marilyn S.; Hyman, Bradley T.; Petersen, Ronald C.; Sano, Mary; Wisniewski, Thomas; Vassar, Robert; Kaye, Jeffrey A.; Henderson, Victor W.; DeCarli, Charles; LaFerla, Frank M.; Brewer, James B.; Miller, Bruce L.; Swerdlow, Russell H.; Van Eldik, Linda J.; Paulson, Henry L.; Trojanowski, John Q.; Chui, Helena C.; Rosenberg, Roger N.; Craft, Suzanne; Grabowski, Thomas J.; Asthana, Sanjay; Morris, John C.; Strittmatter, Stephen M.; Kukull, Walter A.; Psychiatry, School of MedicineImportance: Compared with non-Hispanic White individuals, African American individuals from the same community are approximately twice as likely to develop Alzheimer disease. Despite this disparity, the largest Alzheimer disease genome-wide association studies to date have been conducted in non-Hispanic White individuals. In the largest association analyses of Alzheimer disease in African American individuals, ABCA7, TREM2, and an intergenic locus at 5q35 were previously implicated. Objective: To identify additional risk loci in African American individuals by increasing the sample size and using the African Genome Resource panel. Design, setting, and participants: This genome-wide association meta-analysis used case-control and family-based data sets from the Alzheimer Disease Genetics Consortium. There were multiple recruitment sites throughout the United States that included individuals with Alzheimer disease and controls of African American ancestry. Analysis began October 2018 and ended September 2019. Main outcomes and measures: Diagnosis of Alzheimer disease. Results: A total of 2784 individuals with Alzheimer disease (1944 female [69.8%]) and 5222 controls (3743 female [71.7%]) were analyzed (mean [SD] age at last evaluation, 74.2 [13.6] years). Associations with 4 novel common loci centered near the intracellular glycoprotein trafficking gene EDEM1 (3p26; P = 8.9 × 10-7), near the immune response gene ALCAM (3q13; P = 9.3 × 10-7), within GPC6 (13q31; P = 4.1 × 10-7), a gene critical for recruitment of glutamatergic receptors to the neuronal membrane, and within VRK3 (19q13.33; P = 3.5 × 10-7), a gene involved in glutamate neurotoxicity, were identified. In addition, several loci associated with rare variants, including a genome-wide significant intergenic locus near IGF1R at 15q26 (P = 1.7 × 10-9) and 6 additional loci with suggestive significance (P ≤ 5 × 10-7) such as API5 at 11p12 (P = 8.8 × 10-8) and RBFOX1 at 16p13 (P = 5.4 × 10-7) were identified. Gene expression data from brain tissue demonstrate association of ALCAM, ARAP1, GPC6, and RBFOX1 with brain β-amyloid load. Of 25 known loci associated with Alzheimer disease in non-Hispanic White individuals, only APOE, ABCA7, TREM2, BIN1, CD2AP, FERMT2, and WWOX were implicated at a nominal significance level or stronger in African American individuals. Pathway analyses strongly support the notion that immunity, lipid processing, and intracellular trafficking pathways underlying Alzheimer disease in African American individuals overlap with those observed in non-Hispanic White individuals. A new pathway emerging from these analyses is the kidney system, suggesting a novel mechanism for Alzheimer disease that needs further exploration. Conclusions and relevance: While the major pathways involved in Alzheimer disease etiology in African American individuals are similar to those in non-Hispanic White individuals, the disease-associated loci within these pathways differ.